Role for Reelin in stabilizing cortical architecture

Trends Neurosci. 2010 Sep;33(9):407-14. doi: 10.1016/j.tins.2010.06.001. Epub 2010 Jul 1.

Abstract

Reelin controls the migration of neurons and layer formation during brain development. However, recent studies have shown that disrupting Reelin function in the adult hippocampus induces repositioning of fully differentiated neurons, suggesting a stabilizing effect of Reelin on mature neuronal circuitry. Indeed, Reelin was recently found to stabilize the actin cytoskeleton by inducing cofilin phosphorylation. When unphosphorylated, cofilin acts as an actin-depolymerizing protein that promotes the disassembly of F-actin. Here, a novel hypothesis is proposed whereby decreased Reelin expression in the mature brain causes destabilization of neurons and their processes, leading to aberrant plasticity and aberrant wiring of brain circuitry. This has implications for brain disorders, such as epilepsy and schizophrenia, in which deficiencies in Reelin expression occur.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Depolymerizing Factors / metabolism
  • Actins / metabolism
  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Movement / physiology
  • Cerebral Cortex / cytology*
  • Cerebral Cortex / growth & development
  • Cerebral Cortex / physiology
  • Cytoskeleton / metabolism
  • Epilepsy / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neuronal Plasticity / physiology
  • Neurons / cytology*
  • Neurons / metabolism
  • Receptors, Notch / metabolism
  • Reelin Protein
  • Schizophrenia / metabolism
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction / physiology

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Receptors, Notch
  • Reelin Protein
  • RELN protein, human
  • Serine Endopeptidases